Journal of Alzheimer's Disease - Volume 20, issue s1

Authors: Arendash, Gary W. | Cao, Chuanhai

Article Type: Research Article

Abstract: Epidemiologic studies have increasingly suggested that caffeine/coffee could be an effective therapeutic against Alzheimer's disease (AD). We have utilized a transgenic mouse model for AD in well-controlled studies to determine if caffeine and/or coffee have beneficial actions to protect against or reverse AD-like cognitive impairment and AD pathology. AD mice given caffeine in their drinking water from young adulthood into older age showed protection against memory impairment and lower brain levels of the abnormal protein (amyloid-β; Aβ) thought to be central to AD pathogenesis. Moreover, “aged” cognitively-impaired AD mice exhibited memory restoration and lower brain Aβ levels following only 1–2 …months of caffeine treatment. We believe that the cognitive benefits of chronic caffeine administration in AD mice are due to caffeine itself, and not metabolites of caffeine; this, because our long-term administration of theophylline to AD mice provided no cognitive benefits. In acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Aβ levels – similarly rapid alterations in plasma Aβ levels were seen in humans following acute caffeine administration. “Caffeinated” coffee provided to AD mice also quickly decreased plasma Aβ levels, but not “decaffeinated” coffee, suggesting that caffeine is critical to decreasing blood Aβ levels. Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of Aβ production through suppression of both β- and γ-secretase levels. These results indicate a surprising ability of moderate caffeine intake (the human equivalent of 500 mg caffeine or 5 cups of coffee per day) to protect against or treat AD in a mouse model for the disease and a therapeutic potential for caffeine against AD in humans. Show more

Keywords: Alzheimer's disease, amyloid-β, caffeine, coffee, memory

DOI: 10.3233/JAD-2010-091249

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S117-S126, 2010

Authors: Chen, Xuesong | Ghribi, Othman | Geiger, Jonathan D.

Article Type: Review Article

Abstract: Sporadic Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common neurodegenerative diseases and as such they represent major public health problems. Finding effective treatments for AD and PD represents an unmet and elusive goal largely because these diseases are chronic and progressive, and have a complicated and ill-understood pathogenesis. Although the underlying mechanisms are not fully understood, caffeine, the most commonly ingested psychoactive drug in the world, has been shown in human and animal studies to be protective against AD and PD. One mechanism implicated in the pathogenesis of AD and PD is blood-brain barrier (BBB) …dysfunction and we reported recently that caffeine exerts protective effects against AD and PD at least in part by keeping the BBB intact. The present review focuses on the role of BBB dysfunction in the pathogenesis of AD and PD, caffeine's protective effects against AD and PD, and potential mechanisms whereby caffeine protects against BBB leakage. Show more

Keywords: Alzheimer's disease, blood-brain barrier, caffeine, Parkinson's disease

DOI: 10.3233/JAD-2010-1376

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S127-S141, 2010

Authors: Biessels, Geert Jan

Article Type: Review Article

Abstract: People with diabetes mellitus are at increased risk of cognitive dysfunction. This review explores the relation between caffeine intake, diabetes, cognition and dementia, focusing on type 2 diabetes (T2DM). Epidemiological studies on caffeine/coffee intake and T2DM risk are reviewed. Next, the impact of T2DM on cognition is addressed. Finally, the potential for caffeine to modulate the risk of cognitive decline in the context of diabetes is explored. The conclusion is that, although epidemiological studies indicate that coffee/caffeine consumption is associated with a decreased risk of T2DM and possibly also with a decreased dementia risk, we can at present not be …certain that these associations are causal. For now, recommendations for coffee consumption in individuals with T2DM or pre-diabetic stages are therefore difficult to establish, but it should be acknowledged that caffeine does appear to have several properties that warrant further investigations in this field. Show more

Keywords: Alzheimer's disease, caffeine, coffee, cognition, dementia, diabetes mellitus, epidemiology, insulin, stroke, vascular dementia

DOI: 10.3233/JAD-2010-091228

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S143-S150, 2010

Authors: Kyle, Janet | Fox, Helen C. | Whalley, Lawrence J.

Article Type: Research Article

Abstract: There is interest in age-related cognitive decline and environmental risk factors for Alzheimer's disease (AD). This interest is focused on individual differences in exposure to agents that may harm or protect cognitive function. Caffeine is used as a short acting mental stimulant and may possess longer-term properties that protect against age-related decline and, possibly, AD. The current study aimed to: 1) examine current cognitive function in a narrow age range sample (n=351) without dementia (MMSE>25) who are, by reason of age, entering the period of increased risk of AD; and 2) link cognitive function to self-reported intake of caffeine and …socioeconomic status (SES). Possible confounding by gender, childhood intelligence, education, and symptoms of anxiety and depression was introduced into the statistical model. There were significant differences between SES groups in caffeine intake (p< 0.05) and cognitive performance (p< 0.001). Higher quartiles of caffeine intake were associated with slower digit symbol speed (F =3.38, p< 0.02) but this finding was removed after allowing for SES. The results are discussed in terms of the withdrawal effects of caffeine during cognitive testing and strong links between SES and cognitive performance. No evidence in support of cognitive enhancing effects of caffeine was found. Show more

Keywords: Alcohol, anxiety, attention, caffeine, childhood intelligence, neuroticism, non-verbal reasoning, processing speed, smoking, socioeconomic status, spatial ability, verbal memory

DOI: 10.3233/JAD-2010-1409

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S151-S159, 2010

Authors: Ritchie, Karen | Artero, Sylvaine | Portet, Florence | Brickman, Adam | Muraskin, Jordan | Beanino, Ephrem | Ancelin, Marie-Laure | Carrière, Isabelle

Article Type: Research Article

Abstract: The present study examines the epidemiological evidence for a causal relationship between caffeine consumption and cognitive deterioration in the elderly. Using a population of 641 elderly persons, we examined cognitive functioning, caffeine consumption, magnetic resonance imaging volumetrics, and other factors known to affect cognitive performance. Our findings demonstrate the association between caffeine consumption and lower cognitive change over time to be statistically significant for women only, taking into account multiple confounders, to be dose-dependent and temporarily related (caffeine consumption precedes cognitive change). Mean log transformed white matter lesion/cranial volume ratios were found to be significantly lower in women consuming more …than 3 units of caffeine per day after adjustment for age (−1.23 SD=0.06) than in women consuming 2−3 units (−1.04 SD=0.04) or one unit or less (−1.04 SD=0.07, −35% in cm3 compared to low drinkers). This observation is coherent with biological assumptions that caffeine through adenosine is linked to amyloid accumulation and subsequently white matter lesion formation. The significant relationship observed between caffeine intake in women and lower cognitive decline is highly likely to be a true causal relationship and not a spurious association. Show more

Keywords: Caffeine, cognitive decline, cohort study, white matter lesions

DOI: 10.3233/JAD-2010-1387

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S161-S166, 2010

Authors: Eskelinen, Marjo H. | Kivipelto, Miia

Article Type: Research Article

Abstract: Caffeine has well-known short-term stimulating effects on central nervous system, but the long-term impacts on cognition have been less clear. Dementia and Alzheimer's disease (AD) are rapidly increasing public health problems in ageing populations and at the moment curative treatment is lacking. Thus, the putative protective effects of caffeine against dementia/AD are of great interest. Here, we discuss findings from the longitudinal epidemiological studies about caffeine/coffee/tea and dementia/AD/cognitive functioning with a special emphasis on our recent results from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. The findings of the previous studies are somewhat inconsistent, but most studies (3 …out of 5) support coffee's favorable effects against cognitive decline, dementia or AD. In addition, two studies had combined coffee and tea drinking and indicated some positive effects on cognitive functioning. For tea drinking, protective effects against cognitive decline/dementia are still less evident. In the CAIDE study, coffee drinking of 3–5 cups per day at midlife was associated with a decreased risk of dementia/AD by about 65% at late-life. In conclusion, coffee drinking may be associated with a decreased risk of dementia/AD. This may be mediated by caffeine and/or other mechanisms like antioxidant capacity and increased insulin sensitivity. This finding might open possibilities for prevention or postponing the onset of dementia/AD. Show more

Keywords: Alzheimer's disease, caffeine, coffee, dementia, epidemiology

DOI: 10.3233/JAD-2010-1404

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S167-S174, 2010

Authors: Santos, Catarina | Lunet, Nuno | Azevedo, Ana | de Mendonça, Alexandre | Ritchie, Karen | Barros, Henrique

Article Type: Research Article

Abstract: Alzheimer's disease has emerged in recent decades as a major health problem and the role of lifestyles in the modulation of risk has been increasingly recognized. Recent epidemiological studies suggest a protective effect for caffeine intake in dementia. We aimed to quantify the association between caffeine dietary intake and cognitive decline, in a cohort of adults living in Porto. A cohort of 648 subjects aged ⩾65 years was recruited between 1999–2003. Follow-up evaluation (2005–2008) was carried out on 58.2% of the eligible participants and 10.9% were deceased. Caffeine exposure in the year preceding baseline evaluation was assessed with a validated …food frequency questionnaire. Cognitive evaluation consisted of baseline and follow-up Mini-Mental State Examination (MMSE). Cognitive decline was defined by a decrease ⩾ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95%CI) estimates adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes were computed using Poisson regression. Caffeine intake (> 62 mg/day [3rd third] vs. < 22 mg/day [1st third]) was associated with a lower risk of cognitive decline in women (RR=0.49, 95%CI 0.24–0.97), but not significantly in men (RR=0.65, 95%CI 0.27–1.54). Our study confirms the negative association between caffeine and cognitive decline in women. Show more

Keywords: Caffeine, cohort studies, dementia, gender

DOI: 10.3233/JAD-2010-091303

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S175-S185, 2010

Authors: Santos, Catarina | Costa, João | Santos, João | Vaz-Carneiro, António | Lunet, Nuno

Article Type: Research Article

Abstract: A recent meta-analysis of 4 studies published up to January 2004 suggests a negative association between coffee consumption and Alzheimer's disease, despite important heterogeneity in methods and results. Several epidemiological studies on this issue have been published since then, warranting an update of the insights on this topic. We conducted a systematic review and meta-analysis of published studies quantifying the relation between caffeine intake and cognitive decline or dementia. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort and case-control studies were included. Three independent reviewers selected the studies and extracted …the data on to standardized forms. Nine cohort and two case-control studies were included. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The outcomes of the studies considered for meta-analysis were Alzheimer's disease in four studies, dementia or cognitive impairment in two studies, and cognitive decline in three studies. The summary relative risk (RR) for the association between caffeine intake and different measures of cognitive iimpairment/decline was 0.84 [95% Confidence Interval (95% CI): 0.72–0.99; I2 =42.6%]. When considering only the cohort studies, the summary RR was 0.93 (95% CI: 0.83–1.04, I2 = 0.0%), and 0.77 (95% CI: 0.63–0.95, I2 = 34.7%), if the most influential study was excluded. This systematic review and meta-analysis found a trend towards a protective effect of caffeine, but the large methodological heterogeneity across a still limited number of epidemiological studies precludes robust and definite statements on this topic. and definite statements on this topic. Show more

Keywords: Alzheimer's disease, caffeine, dementia, meta-analysis

DOI: 10.3233/JAD-2010-091387

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S187-S204, 2010

Authors: Prediger, Rui D.S.

Article Type: Review Article

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. Classically, PD is considered to be a motor system disease and its diagnosis is based on the presence of a set of cardinal motor signs (rigidity, bradykinesia, rest tremor) that are consequence of a pronounced death of dopaminergic neurons in the substantia nigra pars compacta. Nowadays there is considerable evidence showing that non-dopaminergic degeneration also occurs in other brain areas which seems to be responsible for the deficits in olfactory, emotional and memory functions that precede the classical motor symptoms …in PD. The present review attempts to examine results reported in epidemiological, clinical and animal studies to provide a comprehensive picture of the antiparkinsonian potential of caffeine. Convergent epidemiological and pre-clinical data suggest that caffeine may confer neuroprotection against the underlying dopaminergic neuron degeneration, and influence the onset and progression of PD. The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. Finally, recent experimental findings have indicated the potential of caffeine in the management of non-motor symptoms of PD, which do not improve with the current dopaminergic drugs. Altogether, the studies reviewed provide strong evidence that caffeine may represent a promising therapeutic tool in PD, thus being the first compound to restore both motor and non-motor early symptoms of PD together with its neuroprotective potential. Show more

Keywords: Adenosine receptors, animal models, caffeine, learning and memory, motor deficits, neuroprotection, olfactory system, Parkinson's disease

DOI: 10.3233/JAD-2010-091459

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S205-S220, 2010

Authors: Costa, João | Lunet, Nuno | Santos, Catarina | Santos, João | Vaz-Carneiro, António

Article Type: Research Article

Abstract: Several studies conducted worldwide report an inverse association between caffeine/coffee consumption and the risk of developing Parkinson's disease (PD). However, heterogeneity and conflicting results between studies preclude a correct estimation of the strength of this association. We conducted a systematic review and meta-analysis of published epidemiological studies to better estimate the effect of caffeine exposure on the incidence of PD. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort, case-control and cross-sectional studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Twenty-six studies …were included: 7 cohort, 2 nested case-control, 16 case-control, and 1 cross-sectional study. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The summary RR for the association between caffeine intake and PD was 0.75 [[95% Confidence Interval (95%CI): 0.68–0.82], with low to moderate heterogeneity (I2 = 28.8%). Publication bias for case-control/cross-sectional studies may exist (Egger's test, p=0.053). When considering only the cohort studies, the RR was 0.80 (95%CI: 0.71–90; I2 =8.1%). The negative association was weaker when only women were considered (RR=0.86, 95%CI: 0.73—1.02; I2 =12.9%). A linear relation was observed between levels of exposure to caffeine and the RR estimates: RR of 0.76 (95%CI: 0.72–0.80; I2 = 35.1%) per 300 mg increase in caffeine intake. This study confirm an inverse association between caffeine intake and the risk of PD, which can hardly by explained by bias or uncontrolled confounding. Show more

Keywords: Caffeine, meta-analysis, Parkinson's disease, relative risk, risk assessment

DOI: 10.3233/JAD-2010-091525

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S221-S238, 2010

Authors: Lara, Diogo R.

Article Type: Review Article

Abstract: Caffeine intake is so common that its pharmacological effects on the mind are undervalued. Since it is so readily available, individuals can adjust their own dose, time of administration and dose intervals of caffeine, according to the perceived benefits and side effects of each dose. This review focuses on human studies of caffeine in subjects with and without psychiatric disorders. Besides the possibility of mild drug dependence, caffeine may bring benefits that contribute to its widespread use. These benefits seem to be related to adaptation of mental energy to the context by increasing alertness, attention, and cognitive function (more evident …in longer or more difficult tasks or situations of low arousal) and by elevating mood. Accordingly, moderate caffeine intake (< 6 cups/day) has been associated with less depressive symptoms, fewer cognitive failures, and lower risk of suicide. However, its putative therapeutic effects on depression and ADHD have been insufficiently studied. Conversely, in rare cases high doses of caffeine can induce psychotic and manic symptoms, and more commonly, anxiety. Patients with panic disorder and performance social anxiety disorder seem to be particularly sensitive to the anxiogenic effects of caffeine, whereas preliminary data suggests that it may be effective for some patients with obsessive compulsive disorder (OCD). The threshold for the anxiogenic effect of caffeine is influenced by a polymorphism of the A2A receptor. In summary, caffeine can be regarded as a pharmacological tool to increase energy and effortful behavior in daily activities. More populational (cross-sectional and prospective) and experimental studies are necessary to establish the role of caffeine intake in psychiatric disorders, especially its putative efficacy on depressive mood and cognitive/attentional disorders. Show more

Keywords: Attention, anxiety, caffeine, cognition, depression, mood

DOI: 10.3233/JAD-2010-1378

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S239-S248, 2010

Authors: Mendonça, Alexandre | Cunha, Rodrigo A.

Article Type: Editorial

DOI: 10.3233/JAD-2010-01411

Citation: Journal of Alzheimer's Disease, vol. 20, no. s1, pp. S249-S252, 2010